Dutch-Waist

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Rijnstate Ziekenhuis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

25 Jul 2024 → ongoing

Decision date (initial)

2024-06-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-501392-81-00

WHO UTN

U1111-1275-9989

ClinicalTrials.gov

NCT06184633

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this randomized controlled trial is to demonstrate superiority of once-weekly 2.4 mg semaglutide s.c. over placebo in achieving sinus rhythm at one year in patients with obesity and first detected, symptomatic persistent atrial fibrillation (AF).

Secondary objectives 11

1. Quantify the impact of weight reduction on AF related symptoms using the modified EHRA score(24) (time frame: week 0, week 52).
2. Quantify effect on weight related parameters (weight, waist circumference, BMI) (time frame: week 0, week 52).
3. Quantify the impact of weight reduction on quality of life using the EQ-5D-5L (time frame: week 0, week 52).
4. Quantify the impact of weight reduction on AF related hospitalizations.
5. Quantify the impact of weight reduction on other cardio-metabolic risk factors, such as hypertension, glycemic control, and lipid profiles.
6. Quantify the impact of the intervention on Work Productivity, using the Work Productivity and Activity Index (time frame: week 0, week 52).
7. Quantify the impact of the intervention on exercise motivation using the Behavioral Regulation and Exercise Questionnaire 2 (time frame: week 0, week 52).
8. Quantify the impact of the intervention on the cost-effectiveness of rhythm control in new-onset persistent AF in obese patients.
9. Quantify the impact of weight reduction on the amount of planned electrical cardioversions.
10. Quantify the impact of the intervention on inflammation using CRP level (time frame: week 0, week 52).
11. Quantify the impact of the intervention on NT-pro BNP levels (time frame: week 0, week 52).

Conditions and MedDRA coding

Atrial fibrillation

Regulatory references

Plan to share IPD

Yes

IPD plan description

Data obtained through this study may be provided to qualified researchers with academic interest in atrial fibrillation. Data will be coded, with no PHI included. Approval of the request and execution of all applicable agreements are prequisites to sharing of data with the requesting party.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Symptomatic, first detected (at maximum 6 months prior to enrollment) persistent AF
2. Age ≥ 18
3. Obesity, as defined as BMI ≥ 30 kg/m2, or BMI ≥27 kg/m2 with the presence of at least one weight related comorbidity (treated or untreated, e.g. hypertension, dyslipidaemia, obstructive sleep apnea, cardiovascular disease)
4. Scheduled electrical cardioversion (ECV)
5. Written informed consent

Exclusion criteria 15

1. Permanent AF
2. Secondary AF due to thyrotoxicosis, infection (e.g. pneumonia) or post-cardiothoracic surgery
3. Current or previous treatment with amiodaron
4. HbA1c ≥ 48 mmol/L, <3 months prior to randomization
5. History of diabetes mellitus type 1 or 2
6. Prior bariatric surgery
7. Use of other anti-obesity medication, <3 months prior to enrollment
8. Contra-indication for, or prior use of a GLP1-receptor agonist
9. History of chronic pancreatitis or acute pancreatitis <6 months
10. Acute coronary syndrome <6 months
11. Severe (grade III) valvular disease
12. Heart failure NYHA class III-IV
13. Participation in another investigational drug or device study in the past 30 days (registry enrollment is allowed)
14. Any condition or therapy, which would make the participant unsuitable for the study (e.g. vulnerable, non-compliance) or life-expectancy <12 months, as judged by the treating physician
15. Female who is pregnant, breastfeeding, intends to become pregnant, or is of child-bearing potential and not using a highly effective contraceptive method.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. For all patients, the one-year rhythm outcome status is ranked according to severity, from the most severe to the least severe outcome, as follows: Arrhythmic death while on Vaughn-Williams class I or III (VW-I/III) anti-arrhythmic drugs (AAD) In Atrial fibrillation (AF) after pulmonary vein isolation (PVI) In AF and on VW-I/III AAD In AF and not on VW-I/III AAD In Sinus Rhythm (SR) after PVI In SR and on VW-I/III AAD In SR and not on VW-I/III AAD
2. The second primary endpoint of the trial is the occurrence of any of the following at or within 12 months after randomization Persistent AF on the ECG at the 12-month visit Catheter ablation for AF Arrhythmic death Any serious adverse event due to an anti-arrhythmic drug This second primary endpoint will be statistically assessed as a binary (yes/no) variable.

Secondary endpoints 20

1. Change in AF related symptoms measured by the modified EHRA score between the index visit and at 12 months after the index visit.
2. Change in quality of life measured by the EQ-5D-5L between the index visit and at 12 months after the index visit.
3. Number of hospitalizations because of an AF recurrence.
4. Number of unscheduled hospital visits because of adverse events of AAD.
5. Number of scheduled electrical cardioversions.
6. Number of unscheduled electrical cardioversions.
7. Number of intravenous chemical cardioversions (using Vaughan-Williams class I drugs).
8. Total number of unscheduled cardioverions
9. Change in waist circumference, measured in cm (time frame: week 0 and 52).
10. Change in weight, measured in % and kg (time frame: week 0 and 52)
11. Change in BMI, measured in kg/m2 (time frame: week 0 and 52).
12. Change in systolic blood pressure, measured in mmHg (time frame: week 0 and 52).
13. Change in diastolic blood pressure, measured in mmHg (time frame: week 0 and 52).
14. Change in HbA1c, measured in % and mmol/L (time frame: week 0 and 52)
15. Change in lipids (total cholesterol, LDL, HDL and triglycerides), measured in mmol/L (time frame: week 0 and 52)
16. Change in CRP, measured in mg/L (time frame: week 0 and 52).
17. Change in NT-pro BNP, measured pmol/L (time frame: week 0 and 52)
18. Change in work productivity measured by the Work Productivity and Activity Index, between the index visit and at 12 months after the index visit.
19. Change in exercise motivation using the Behavioral Regulation and Exercise Questionnaire 2 between the index visit and at 12 months after the index visit.
20. Difference in total cost of all healthcare expenditures related to the management of atrial fibrillation, in Euros.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Rijnstate Ziekenhuis

Sponsor organisation

Stichting Rijnstate Ziekenhuis

Address

Wagnerlaan 55

City

Arnhem

Postcode

6815 AD

Country

Netherlands

Scientific contact point

Organisation

Stichting Rijnstate Ziekenhuis

Contact name

Ron Pisters

Public contact point

Organisation

Stichting Rijnstate Ziekenhuis

Contact name

Ron Pisters

Locations

1 EU/EEA country · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications